Effect of cyclic dipeptides containing histidine on pentobarbital narcosis.
We examined the effect of cyclo (His-Pro) and its analogs on pentobarbital narcosis in mice. Cyclo (His-Pro), 500 nmol/mouse, administered via intracerebroventricular (i.c.v.) route significantly prolonged the sleeping time. Methylation of histidine in the structure of cyclo (His-Pro) did not increase the activity of cyclo (His-Pro). Some of other cyclo (His-Pro) analogs, of which proline was replaced with other amino acids, cyclo (His-Phe), cyclo (His-Tyr), cyclo (His-His) and cyclo (D-His-Leu) produced significant prolongation of the sleeping time as compared with cyclo (His-Pro). These results suggest that cyclo (His-Pro) has opposing effect to that of thyrotropin releasing hormone (TRH) and the prolongation of pentobarbital narcosis by cyclic dipeptides might be caused by their central action.
D000818:Animals; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D010424:Pentobarbital / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D010456:Peptides, Cyclic; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital; C015924:histidyl-proline diketopiperazine